One-hundred eighteen patients with stage IIB-IV non-small cell lung cancer were treated with isotoxically escalated concurrent chemoradiation to median prescribed doses of 64.5 and 67.6 Gy in 30 fractions over 5 (n Z 36) or 6 weeks (n Z 82). Toxicity was acceptable for both schedules. Overall survival was longer in 6-week than in 5-week patients (median, 41.2 vs 22.1 months; hazard ratio, 0.56; 95% confidence interval, 0.32-0.98; P Z .04). Progression-free survival was also longer in 6-week patients (median, 21.1 vs 8.0 months; hazard ratio, 0.53; 95% confidence interval, 0.33-0.86; P Z .01).Purpose: The IDEAL-CRT phase 1/2 multicenter trial of isotoxically dose-escalated concurrent chemoradiation for stage II/III non-small cell lung cancer investigated two 30-fraction schedules of 5 and 6 weeks' duration. We report toxicity, tumor response, progression-free survival (PFS), and overall survival (OS) for both schedules, with long-term follow-up for the 6-week schedule. Methods and Materials: Patients received isotoxically individualized tumor radiation doses of 63 to 71 Gy in 5 weeks or 63 to 73 Gy in 6 weeks, delivered concurrently with 2 cycles of cisplatin and vinorelbine. Eligibility criteria were the same for both schedules.Results: One-hundred twenty patients (6% stage IIB, 68% IIIA, 26% IIIB, 1% IV) were recruited from 9 UK centers, 118 starting treatment. Median prescribed doses were 64.5 and 67.6 Gy for the 36 and 82 patients treated using the 5-and 6-week schedules. Grade 3 pneumonitis and early esophagitis rates were 3.4% and 5.9% overall and similar for each schedule individually. Late grade 2 esophageal toxicity occurred in 11.1% and 17.1% of 5-and 6-week patients. Grade 4 adverse events occurred in 17 (20.7%) 6-week patients but no 5-week patients. Four adverse events were grade 5, with 2 considered radiation therapy related. After median follow-up of 51.8 and 26.4 months for the 6-and 5-week schedules, median OS was 41.2 and 22.1 months, respectively, and median PFS was 21.1 and 8.0 months. In exploratory analyses, OS was significantly associated with schedule (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.32-0.98; P Z .04) and fractional clinical/internal target volume receiving 95% of the prescribed dose (HR, 0.88; 95% CI, 0.77-1.00; P Z .05). PFS was also significantly associated with schedule (HR, 0.53; 95% CI, 0.33-0.86; P Z .01). Conclusions: Toxicity in IDEAL-CRT was acceptable. Survival was promising for 6-week patients and significantly longer than for 5-week patients. Survival might be further lengthened by following the 6-week schedule with an immune agent, motivating further study of such combined optimized treatments.